End of life care for cancer patients differs in US and Canada

ScienceDaily (May 18, 2011) — In the United States, older patients with advanced lung cancer make much less use of hospital and emergency room services at the end of life than their counterparts in Ontario but use far more chemotherapy, according to a study published May 18th online in the Journal of the National Cancer Institute.

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Government-financed health care covers elderly patients in both Canada and the U.S., but coverage at the end of life differs. In the U.S., Medicare covers hospice care for qualified patients. Ontario, the most populous Canadian province, has no hospice program comparable to what exists in the U.S. but provides palliative care through inpatient acute care units, outpatient services and home health care.

To compare end-of-life care between the two systems, Joan L. Warren, Ph.D., of the National Cancer Institute and colleagues used U. S. Surveillance, Epidemiology, and End Results (SEER)-Medicare data and data from the Ontario Cancer Registry. They identified patients age 65 and older who died with non-small cell lung cancer (NSCLC) during 1999-2003 and reviewed health claims from their last 5 months of life to collect data on chemotherapy, emergency room use, hospitalizations, and supportive care in both short-term (less than 6 months) and longer-term (6 months or more) survivors.

Patients in both countries used health-care services extensively, particularly in the last month of life. Ontario patients had hospital admissions and used emergency room services at rates that were statistically significantly greater than those of U.S. patients. More than twice as many Ontario patients died in hospital (e.g., 48.5% of short-term survivors compared to 20.4% in the U.S.) even though a majority of Ontario patients have reported that they would prefer to die at home. In each of the last 5 months, chemotherapy rates were statistically significantly higher among SEER-Medicare patients than among the Ontario patients.

The authors note that these findings partly support the commonly held view that U.S. physicians have a more aggressive attitude toward treatment and that patients in the U.S. tend to receive more intensive health-care services. However, U.S. patients can enroll in hospice services, an option not readily available in Ontario. The authors conclude that the lack of hospice services contributes to higher rates of hospital and emergency room visits and in-hospital deaths among Ontario patients.

The findings, they write, "will inform health planners and policy makers in each country regarding current patterns of end-of-life care and where there may be opportunities for changing practice patterns or programs."

In an editorial, David Goodman, M.D., of the Dartmouth Institute for Health Policy and Clinical Practice, notes that end-of-life care varies not only between the U.S. and Ontario, but also from region to region within the U.S. and Canada. Even more important, he writes, patient preferences varies from one individual to another and these preferences are often unheard: "Quality in end-of-life care will continue to elude us if we assume that societal average preferences indicate the care individual patients want and need," he writes.

Goodman argues that the best care at the end of life is care in which the patient participates in the decision-making. "The solution…is not to blindly drive systems towards greater use of hospice and palliative care services. It is to improve decision quality so that patients can make an informed choice with an understanding of the patient experiences associated with active curative care, with supportive care, or with concurrent

Enzyme may drive breast cancer growth

ScienceDaily (May 20, 2011) — A recently discovered enzyme drives the production of a potent form of estrogen in human breast cancer tissue, researchers from the University of Illinois at Chicago College of Medicine have found.

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The extra-strength estrogen, called estradiol, then drives the production of even more enzyme, in what may be a lethal feed-forward mechanism. Estradiol has been implicated in exacerbating tumor growth in breast cancer.

The research is published in the May issue of the journal Molecular Endocrinology.

Scientists had observed the increased production of an unknown protein in ovarian tissue in response to estrogen. UIC researchers under the direction of Geula Gibori, UIC professor of physiology and biophysics, then purified the protein and cloned its gene. Several laboratories established that it is an enzyme that converts a weak estrogen, estrone, to the much more potent estradiol.

The UIC researchers then examined the production of the enzyme in a line of breast cancer cells known to respond to estrogen levels.

"Estradiol up-regulates the very enzyme that produces estradiol, creating a positive cycle where this potent form of estrogen is being produced over and over again, sustaining its own production," said Aurora Shehu, UIC postdoctoral research associate in physiology and biophysics and first author of the study.

In human breast tissue, the researchers found a "dramatic" up-regulation in the cancerous cells but not in the surrounding benign tissue, said Gibori, who is principal investigator on the study. The surrounding tissue, however, is a rich source of the estrone that the enzyme needs to produce more estradiol, she said.

The researchers were able to show how estradiol turns on the gene that produces the enzyme, and that this activation also required at least one other known regulatory factor.

They found that tamoxifen, a drug widely used to inhibit breast cancer growth, prevents estradiol's stimulation of the enzyme and thus may shut down local production of estradiol in breast cancer cells.

"Breast cancer tumors with this enzyme are likely to be a much more aggressive and potentially deadly type of cancer," Gibori said. "Identifying this enzyme and how its expression is turned on gives medical researchers potential targets for disrupting the lethal production of estradiol in breast cancers."

The enzyme is a promising therapeutic target because blocking it may halt production only of the dangerous estradiol, which would reduce the side effects seen with other drugs that inhibit production of many estrogen-related compounds, Gibori said.

This study was supported by grants from the National Institutes of Health. Y. Sangeeta Devi, Kristin Luther, Julia Halpern, Jamie Le, Jifang Mao, Rachel Duan and Jonna Frasor from UIC and Constance Albarracin of the University of Texas, Houston, also contributed to the study.

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New treatment regimen shows clinical benefit in advanced colon cancer

ScienceDaily (May 21, 2011) — A new treatment regimen for patients with metastatic colon cancer appears to offer clinical benefit even when used after multiple other treatments have failed, say research physicians at Georgetown Lombardi Comprehensive Cancer Center, a part of Georgetown University Medical Center.

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The research team found that combining a PARP inhibitor with chemotherapy (temozolomide) offers significant benefit in patients who had no further treatment options. However, the study is small, and does not include a comparison arm, so further investigation is needed, they add. The study will be presented in an oral session on Saturday, June 4th, at the 2011 annual meeting of the American Society of Clinical Oncology in Chicago.

PARP, short for "poly (ADP-ribose) polymerase" is a key part of a cell's DNA repair apparatus, and is important for protecting our normal cells against DNA damage. However, cancer cells become resistant to chemotherapy in part by increasing PARP expression and thus rapidly repairing DNA damage intentionally caused by chemotherapy. PARP inhibitors are designed to overcome a cancer cell's ability to repair the damaged DNA. (They are showing promise in both breast and ovarian cancers, and are being studied in a variety of other cancer types).

In this clinical study, doctors administered a potent DNA-damaging chemotherapy, temozolomide, with a PARP inhibitor called ABT-888. The theory is that ABT-888 will diminish the ability of these cancer cells to fix the damage that was just inflicted by the temozolomide, pushing the cancer into a death spiral.

"This is a classic one-two punch: the chemotherapy damages the cancer cells and the PARP inhibitor prevents it from fixing itself, leaving the cell to die," says lead author, Michael Pishvaian, M.D., Ph.D., an assistant professor at Georgetown Lombardi.

This single-arm, phase II study enrolled 49 patients with metastatic disease who were not eligible for surgery and had exhausted all of the standard therapies currently used. Despite having advanced cancer, all study participants were still active at work or home. Researchers found the drug combination controlled cancer growth for nearly six months in 23 percent of the patients, with two patients having a significant reduction in their tumor burden (partial response).

Pishvaian explains, "The treatment was extremely well tolerated, so to have a period of six months with no tumor growth, but also no significant side effects was really meaningful for the patients."

In addition, researchers were able to collect samples of the patients' tumors for further molecular analysis. "By testing tissue samples and identifying their molecular fingerprints, perhaps we can identify which patient subgroups are most likely to respond to this new therapeutic combination," concludes Pishvaian.

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Yoga improves quality of life in women with breast cancer undergoing radiation therapy, study finds

ScienceDaily (May 18, 2011) — For women with breast cancer undergoing radiation therapy, yoga offers unique benefits beyond fighting fatigue, according to new research from The University of Texas MD Anderson Cancer Center.

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While simple stretching exercises improved fatigue, patients who participated in yoga that incorporated yogic breathing, postures, meditation and relaxation techniques into their treatment plan experienced improved physical functioning, better general health and lower cortisol (stress hormone) levels. They also were better able to find meaning in their cancer experience.

The findings, to be presented next month in an oral session at the 47th annual meeting of the American Society of Clinical Oncology by Lorenzo Cohen, Ph.D., professor and director of the Integrative Medicine Program at MD Anderson, are the latest in an ongoing effort to scientifically validate the age-old belief that mind-body interventions have a beneficial impact on the health of cancer patients. The research was conducted in collaboration with India's largest yoga research institution, Swami Vivekananda Yoga Anusandhana Samsthana in Bangalore, India.

The study assessed, for the first time, yoga benefits to cancer patients by comparing their experience with patients in an active control group who integrated simple, generic stretching exercises into their lives. "The combination of mind and body practices that are part of yoga clearly have tremendous potential to help patients manage the psychosocial and physical distress associated with treatment and life after cancer, beyond the benefits of simple stretching," said Cohen.

To conduct the study, 163 women with breast cancer (stage 0-3) averaging 52 years of age were randomized to one of three groups: 1) yoga; 2) simple stretching; or 3) no instruction in yoga or stretching. Participants in the yoga and stretching groups attended sessions specifically tailored to breast cancer patients for one hour three days a week throughout their six weeks of radiation treatment.

Participants were asked to report on their quality of life, including fatigue, daily functioning, benefit finding, depression and spirituality. Saliva samples were collected and electrocardiogram tests were administered at baseline, end of treatment, and at one, three and six months post-treatment.

After completing radiation treatment, only the women in the yoga and stretching groups reported a reduction in fatigue. At one, three and six months after radiation therapy, women who practiced yoga during the treatment period reported greater benefits to physical functioning and general health. They were more likely to perceive positive life changes from their cancer experience than either other group.

Women who practiced yoga also had the steepest decline in their cortisol across the day, indicating that yoga had the ability to regulate this stress hormone. This is particularly important because higher stress hormone levels throughout the day, known as a blunted circadian cortisol rhythm, have been linked to worse outcomes in breast cancer.

According to Cohen, developing a yoga practice also helps patients after completing cancer treatment. "The transition from active therapy back to everyday life can be very stressful as patients no longer receive the same level of medical care and attention. Teaching patients a mind-body technique like yoga as a coping skill can make the transition less difficult."

Through a grant from the National Cancer Institute -- the largest ever awarded for the study of yoga in cancer -- Cohen and his team will next conduct a Phase III clinical trial in women with breast cancer to further determine the mechanisms of yoga that lead to improvement in physical functioning, quality of life, and biological outcomes during and after radiation treatment. A secondary aim of the trial, but one of great importance, stressed Cohen, is assessing cost efficiency analysis for the hospital, health care usage costs in general, and examining work productivity of patients.

MD Anderson recognizes the growing body of research indicating that relaxation-based interventions can contribute to the well-being of people with cancer. Through the Integrative Medicine Program, complementary therapies, such as yoga, are offered at MD Anderson's Integrative Medicine Center, and are used in concert with mainstream care to manage symptoms, relieve stress, enhance quality of life, and improve outcomes for patients and their caregivers. MD Anderson's Integrative Medicine faculty also conduct research in the biological and behavioral effects of mind-body based interventions; the anti-cancer potential of natural compounds; and, acupuncture to treat common cancer treatment-related side effects.

In addition to Cohen, other MD Anderson researchers contributing to this study include: Kavita Chandwani, M.D., former senior research coordinator and yoga teacher; Robin Haddad, M.P.H. , research coordinator, George Perkins, M.D. in the Department of Radiation Oncology; Amy Spelman, Ph.D., Kayla Johnson, B.S. and Adoneca Fortier, B.S., all staff in the Integrative Medicine Program; Banu Arun, M.D., in the Department of Breast Medical Oncology; and Qi Wei, M.S., Sr. Statistical Analyst. Clemens Kirschbaum, Ph.D. contributed from the Technical University of Dresden, Dresden, Germany. Collaborators from SVYASA include NV Raghuram, B.E.; R. Nagarathna, M.D., and HR Nagendra, Ph.D., founder.

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Recurring cancers in women with a history of breast cancer differ from the original tumors

ScienceDaily (May 18, 2011) — When women with a history of breast cancer learn they have breast cancer again, one of the first questions they and their doctors ask is: Has my cancer come back, or is this a new case? Now, new data from Fox Chase Cancer Center suggest that both new and recurring cancers will differ significantly from the original tumors, regardless of how many months or years women spent cancer-free, and doctors should tailor treatment to the specific qualities of the second tumor, regardless of whether it's old or new.

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Anita Patt, MD, surgical oncology fellow at Fox Chase and lead author on the study, will be presenting the findings at the 2011 Annual Meeting of the American Society of Clinical Oncology on Monday, June 6.

"There tends to be a stigma and a lot of anxiety about the word 'recurrence,'" says Richard J. Bleicher, MD, FACS, attending surgeon at Fox Chase and senior author on the study. "Sometimes women will worry more if they believe their original cancer is back, meaning they didn't 'beat it' the first time around. These findings suggest they should not get hung up on that idea, because any subsequent diagnosis -- whether it's a recurrence or a new tumor -- will look significantly different from their first cancer."

In women with a history of breast cancer, doctors often approach new tumors differently depending on whether they believe it's a recurrence of the first tumor, or a totally new one, Bleicher explains. But there are no official ways to distinguish between the two types, so doctors typically rely on a few criteria, then form their own opinion based on an "overall gestalt," he says.

One of the criteria doctors have used to distinguish between new and recurring cancers is the amount of time women spent cancer-free, reasoning that the longer the time between the two tumors, the more likely the second one is to be an entirely new case.

To investigate if this and other criteria indeed distinguish new and recurring tumors, Bleicher, Patt, and their colleagues looked at data collected from 4,420 women with a history of breast cancer. Two-hundred and thirty five women were eventually diagnosed with another tumor in the same breast, suggesting it could be a recurrence.

However, when the researchers compared the first and second tumors, they saw that 89% differed in at least one key characteristic that could potentially affect treatment or prognosis, regardless of whether the second tumors were new cases or a recurrence of the original cancer. Sixty percent of the second tumors differed from the first by at least 2 or more criteria, including whether or not it would respond to hormones, how it was diagnosed, and whether at least 25 percent of the tumor was confined to the ducts, and therefore less able to spread throughout the body.

Half of the women experienced a second tumor within 60.5 months of their first. And, importantly, the amount of time they spent cancer-free appeared to have no bearing on whether the two tumors differed in any key characteristics.

The findings suggest that patients and doctors shouldn't spend much time determining if the second tumor is a recurrence of the first, or a totally new entity, says Bleicher, and should instead tailor treatment to the specific qualities of the second tumor, regardless of whether it's old or new.

"When a patient comes back with a relapse, whether it's a new tumor or a recurrence, it really doesn't make a difference," he says. "We treat them both as potentially curable."

Co-authors on the study include Tianyu Li, Massimo Cristofanilli, and Elin Sigurdson, from Fox Chase and Gary Freedman from the Hospital of the University of Pennsylvania.

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Lymphocyte count indicates prognosis of patients with renal cell carcinoma, researchers find

ScienceDaily (May 18, 2011) — Each year, kidney cancer is diagnosed in nearly 60,000 people in the U.S. Many of these patients undergo surgery to remove the affected kidney, but this procedure can be risky for the elderly and those who have other health problems. Unfortunately, the prognosis of kidney cancer patients often cannot be determined until tumor samples are surgically removed and evaluated. Now, researchers at Fox Chase Cancer Center have discovered that the lymphocyte count--which is routinely measured in laboratory tests--is a simple and effective prognostic indicator in patients with renal cell carcinoma (RCC).

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Sunil Saroha, MD, medical oncology fellow at Fox Chase and lead author on the study, will be presenting the findings at the 2011 Annual Meeting of the American Society of Clinical Oncology on Sunday, June 5.

"There has been this need for looking at prognostic markers that are available prior to surgical procedures," says Saroha. "It would be nice to know before the surgery if the tumor is going to be aggressive and how aggressive we need to be, with the goal of individualizing therapies."

The level of lymphocytes, a type of white blood cell, was one possible prognostic indicator considered by Saroha, Tahseen Al-Saleem, MD, a cancer pathologist at Fox Chase, and their colleagues. RCC patients generally have a worse prognosis if they have a suppressed immune system, which is indicated by low lymphocyte levels.

By evaluating data from more than 500 patients with the most common form of RCC -- called clear cell RCC -- who had their kidneys surgically removed at Fox Chase between 1994 and 2009, Al-Saleem and his colleagues found a clear relationship between low lymphocyte counts within three months prior to surgery and a poor prognosis.

The researchers found that lower lymphocyte levels were associated with a higher tumor grade, a higher pathologic tumor stage, the presence of distant metastases, and a higher TNM stage -- a combined indicator of tumor stage, spread to regional lymph nodes, and distant metastasis. They also found that low counts were associated with a lower overall survival rate, even when they accounted for patient age, tumor stage and metastasis.

Although these findings should be explored further in prospective research studies, the researchers suggest that the lymphocyte count could factor into doctors' treatment decisions. "This simple test can really help us identify patients at the outset who are at risk of very aggressive disease and who may not do well with current therapies," Saroha says. For example, if a young RCC patient has a low lymphocyte count but is otherwise healthy, a doctor may decide to pursue more aggressive therapies, such as surgery and chemotherapy.

"On the other hand, the test may also identify patients who may not need as aggressive therapies as usual," Saroha adds. For example, about half of RCC patients are over 60 years old, and if one of these patients has other health problems and a normal lymphocyte count, a doctor may decide to monitor the patient rather than perform surgery. "The test may help individualize therapies, change clinical decisions and add therapies before or after the surgery," Saroha says.

Saroha also emphasizes the need for more studies that focus on only one subtype of RCC, as in this study. Previous studies have clumped together different subtypes of RCC patients, even though there could be significant differences between them.

Co-authors on the study include Robert Uzzo, Gary Hudes, Elizabeth Plimack, and Karen Ruth from Fox Chase.

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Ex-Dallas Maverick survives rare form of leukemia thanks to experimental drug treatment

ScienceDaily (May 19, 2011) — Ray Johnston's goal in three years is for his band to sell out at the 1,600-seat House of Blues in Dallas. In eight years, he wants to pack the 6,400-seat Verizon Theatre in Grand Prairie, and by 2030, to play to tens of thousands of fans at Cowboys Stadium in Arlington.

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Mr. Johnston's unmentioned goal, though, is to live another year after battling leukemia for the past seven. Despite four relapses, the former Dallas Mavericks basketball player is enjoying life as a rising musician in The Ray Johnston Band.

Although he credits God for his recovery, Mr. Johnston also gives thanks to Dr. Robert Collins, director of the Bone Marrow Transplantation/Hematologic Malignancies Program at UT Southwestern Medical Center, and the experimental drug that has killed his rare, stubborn form of cancer called acute promyelocytic leukemia.

"It's got to be inspiring to Dr. Collins to see that I'm alive because I'm supposed to be done by now," Mr. Johnston said of his painful yet rewarding journey, which was chronicled last year in an HDNet series called "Ray Johnston Band: Road Diaries."

Today, Mr. Johnston's self-described "happy rock" Dallas band is working on its second CD and booking about 100 shows a year. "My primary goal is to keep playing," Mr. Johnston said.

Tamibarotene, the drug that's kept the 32-year-old musician alive, is a retinoid drug that induces cancer cells to differentiate into mature cells and eventually die. Available only in clinical trials in the U.S., tamibarotene was sought for Mr. Johnston under a compassionate use protocol since he did not qualify for those studies and other treatments had been exhausted. The drug, approved only in Japan for cancer treatment, is being developed domestically by CytRx.

"It's amazing that he's still doing so well," said Dr. Collins, professor of internal medicine and senior author of a report on this case published online April 11 in the Journal of Clinical Oncology. "This drug happens to be just right for him."

Mr. Johnston's treatment with tamibarotene, which is considered 10 times more potent than all-trans retinoic acid, another retinoid commonly used to treat this type of leukemia, began in December 2009. He took the drug twice daily for 56 days, followed by a two-week break. Since then, Mr. Johnston has been taking the drug 28 days on, 28 off.

On April 18, he returned to UT Southwestern for a positron emission tomography (PET) scan, which showed his cancer had not relapsed for the fifth time.

"The type of acute leukemia he has is very rare. It's usually curable with current therapies, but as it relapses it becomes more resistant and harder to treat," said Dr. Collins.

Gambling on life, and success as a musician, doesn't scare the Alabama native who once dreamed of a professional basketball career. But cancer ended his NBA stint, which began when he won a spot on the Dallas Mavericks summer league roster during a Hoop It Up tournament in 2004.

Mr. Johnston didn't even know he had leukemia until that August, when he injured his leg in a pick-up game. He was diagnosed with compartment syndrome, a condition in which pressure in the muscle builds to dangerous levels. Following surgery, doctors were unable to control bleeding. They soon discovered that Mr. Johnston's body was riddled with advanced leukemia.

His treatment included chemotherapy, surgery and a bone marrow transplant. Mr. Johnston's type of leukemia, which affects soft tissues rather than blood and bone marrow, represents just 5 percent to 8 percent of acute myelogenous leukemia, the most common form of the disease.

Discouraged by failing treatments and the thought of his first bone marrow transplant, he nearly gave up hope. In 2006, a recommendation from a friend led him to Dr. Collins and UT Southwestern.

"When you achieve a life milestone that you're not supposed to, when you hug it out, you can see and feel Dr. Collins drop a tear on your shoulder. That's life. That's real," said Mr. Johnston.

Reality for this cancer survivor also means getting serious about music. Mr. Johnston has a lot of work ahead after launching the six-member band in September 2009. Some of the band's performances raise money for The Ryan Gibson Foundation, a Dallas-based nonprofit dedicated to leukemia research.

One of the songs on the band's first CD, "Sweet Tooth," is Rise & Go, based on a verse in the Bible, Luke 17:19. Mr. Johnston said it sums up "my last seven years."

"Wake up and I go outside, I see my blue sky, I'm happy to be alive … I got a tough upper lip, but a bottom little broken heart. When I look into the sky, I see my Maker's eyes. That's when I know my Plan B for eternity is strong as gold, so I rise and go.

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